SP100030
Dual NF-kB / AP-1 inhibitor / SP100030 is a potent dual inhibitor of NF-kB- and AP-1-mediated gene expression (IC50’s = 50 nM for both in transfected Jurkat T-cells).1 It was able to specifically block IL-2 and IL-8 in Jurkat T-cells (IC50’s = 30 nM for both).1 SP100030 treatment significantly decreased arthritis severity in DBA/1J mice.2 It selectively inhibited CD8(+) T-cells and mRNA expression of TH1 and Th2 cytokines in a rat model of asthma but did not inhibit allergen-induced eosinophilia and bronchial hyperresponsiveness.3 SP100030 ameliorated muscle wasting in a cancer cachexia rat model.4 SP100030 suppression of T cell activation has been attributed to targeting of XPO1 (with minimal impact on nuclear export and cell viability).5
Biochemicals & reagents
154563-54-9
2-Chloro-4-(trifluoromethyl)pyrimidine-5-N-(3’,5’-bis(trifluoromethyl)phenyl)carboxamide
1) Sullivan et al. (1998), 2-Chloro-4-(trifluoromethyl)pyrimidine-5-N-(3',5'-bis(trifluoromethyl)phenyl)carboxamide: A Potent Inhibitor of NF-kB- and AP-1-Mediated Gene Expression Identified Using Solution-Phase Combinatorial Chemistry; J. Med. Chem. 41 413 2) Gerlag et al. (2000), The effect of a T cell-specific NF-kappa B inhibitor on in vitro cytokine production and collagen-induced arthritis; J. Immunol. 165 1652 3) Huang et al. (2001), A novel transcription factor inhibitor, SP100030, inhibits cytokine gene expression, but not airway eosinophilia or hyperresponsiveness in sensitized and allergen-exposed rats; Br. J. Pharmacol. 134 1029 4) Moore-Carrasco et al. (2007), The AP-1/NF-kappaB double inhibitor SP100030 can revert muscle wasting during experimental cancer cachexia; Int. J. Oncol. 30 1239 5) Chen et al. (2024), Targeting the chromatin binding of exportin-1 disrupts NFAT and T cell activation; Nat. Chem. Biol. 20 1260
-20°C
TARGET: Transcription factor -- PATHWAY: Transcription; Cytokine; NFkappaB -- DISEASE AREA: Inflammation